NM_001350709.2:c.1650T>G

Variant names:

• chr7-14574332-A-C
• rs1191034334
• NM_001350709.2:c.1650T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001350709.2(DGKB):​c.1650T>G​(p.Ile550Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DGKB NM_001350709.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.17
• Publications: 3 publications found

Genes affected

DGKB (HGNC:2850): (diacylglycerol kinase beta) Diacylglycerol kinases (DGKs) are regulators of the intracellular concentration of the second messenger diacylglycerol (DAG) and thus play a key role in cellular processes. Nine mammalian isotypes have been identified, which are encoded by separate genes. Mammalian DGK isozymes contain a conserved catalytic (kinase) domain and a cysteine-rich domain (CRD). The protein encoded by this gene is a diacylglycerol kinase, beta isotype. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.908

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350709.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKB	NM_001350709.2	MANE Select	c.1650T>G	p.Ile550Met	missense	Exon 20 of 26	NP_001337638.1	B5MBY2
	DGKB	NM_001350705.1		c.1653T>G	p.Ile551Met	missense	Exon 20 of 26	NP_001337634.1	Q9Y6T7-1
	DGKB	NM_001350706.2		c.1653T>G	p.Ile551Met	missense	Exon 20 of 26	NP_001337635.1	Q9Y6T7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKB	ENST00000402815.6	TSL:5 MANE Select	c.1650T>G	p.Ile550Met	missense	Exon 20 of 26	ENSP00000384909.1	B5MBY2
	DGKB	ENST00000406247.7	TSL:1	c.1653T>G	p.Ile551Met	missense	Exon 19 of 24	ENSP00000386066.3	Q9Y6T7-2
	DGKB	ENST00000399322.7	TSL:5	c.1653T>G	p.Ile551Met	missense	Exon 19 of 25	ENSP00000382260.3	Q9Y6T7-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248840 AF XY: 0.00000741

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460908 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726726

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39600

South Asian (SAS) AF: 0.00 AC: 0 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111550

Other (OTH) AF: 0.00 AC: 0 AN: 60342

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152116 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74310

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		2.2
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.014	D
Polyphen		0.99	D
Vest4		0.90
MutPred		0.76		Gain of helix (P = 0.0349)
MVP		0.49
MPC		1.0
ClinPred		0.92	D
GERP RS		2.8
Varity_R		0.53
gMVP		0.74
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1191034334; hg19: chr7-14613957;